A major goal of this project is to localize age-related neurochemical changes within hippocampal circuitry and to address specific hypotheses about the bases for aging in these systems. Studies using quantitative in vitro autoradiography are designed to examine binding sites where effects of aging have been found in our previous work using homogenate assays of whole hippocampus (muscarinic and N-methyl-D-aspartate sites). Additional type of receptors associated with the cholinergic and excitatory amino acid systems will also be examined. In conjunction with these studies, subtypes of somatostatin binding sites will be assessed. The major hypothesis in this work is that brain aging in hippocampal/cortical circuitry will be most pronounced in old rats that are cognitively-impaired relative to both young and unimpaired aged rats. A second goal is to further examine the regulation and release of opioid peptides in the aged hippocampus. A basis for the age-related dysregulation of dynorphin in dentate granule cells (elevated dynA(1-8) immunoreactivity and prodynorphin MRNA) will be examined in young rats subjected to treatments designed to mimic the effects of aging on hippocampal afferent systems. In addition, a radioligand binding assay in the in vitro hippocampal slice will also be used to determine whether dynorphin release evoked by mossy fiber stimulation is altered in the aged brain. A final goal of the project will be to continue behavioral work aimed at identifying individual differences in young adult rats that may serve as predictors of cognitive function and brain aging in later life.